ArticleJournal of cachexia, sarcopenia and muscle2019
Citrulline stimulates muscle protein synthesis, by reallocating ATP consumption to muscle protein synthesis.
Article in Journal of cachexia, sarcopenia and muscle, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Impact of a short-term nitrate and citrulline co-supplementation on sport performance in elite rowers: a randomized, double-blind, placebo-controlled crossover trial.European journal of applied physiology · 2024Trial
- Trial
- Effects of Duodenal Infusion of L-Citrulline on Plasma Metabolism, Fecal Microbiota Structure, and Reproductive Hormones in Ewes.Life (Basel, Switzerland) · 2026Article
- Potential role of L-citrulline in regulating exercise performance and muscle protein metabolism.NPJ science of food · 2026Review
- Review
- Integrated multi-omics reveals potential regulatory mechanisms of meat quality.Food chemistry. Molecular sciences · 2025Article
- The Emerging Role of Citrulline and Theanine in Health and Disease: A Comprehensive Review.Nutrients · 2025Review
- Article
- Running a genetic stop sign accelerates oxygen metabolism and energy production in horses.Science (New York, N.Y.) · 2025Article
- Understanding metabolic plasticity at single cell resolution.Essays in biochemistry · 2024Review
- Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.Life (Basel, Switzerland) · 2024Article
- A botanical extract blend ofFrontiers in nutrition · 2024Article
- Adenosine triphosphate induced cell death: Mechanisms and implications in cancer biology and therapy.World journal of clinical oncology · 2023Review
- Supplementing L-Citrulline Can Extend Lifespan inBiomolecules · 2023Article
- Supplementation with Nitric Oxide Precursors for Strength Performance: A Review of the Current Literature.Nutrients · 2023Review
- L-Citrulline Supplementation Reduces Blood Pressure and Myocardial Infarct Size under Chronic Intermittent Hypoxia, a Major Feature of Sleep Apnea Syndrome.Antioxidants (Basel, Switzerland) · 2022Article
- Plasma metabolome study reveals metabolic changes induced by pharmacological castration and testosterone supplementation in healthy young men.Scientific reports · 2022Article
- Citrulline protects human retinal pigment epithelium from hydrogen peroxide and iron/ascorbate induced damages.Journal of cellular and molecular medicine · 2022Article
- Dietary supplementation with inosine-5'-monophosphate improves the functional, energetic, and antioxidant status of liver and muscle growth in pigs.Scientific reports · 2022Article
- Citrulline, Biomarker of Enterocyte Functional Mass and Dietary Supplement. Metabolism, Transport, and Current Evidence for Clinical Use.Nutrients · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnimal studies and clinical data support the interest of citrulline as a promising therapeutic for sarcopenia. Citrulline is known to stimulate muscle protein synthesis, but how it affects energy metabolism to support the highly energy-dependent protein synthesis machinery is poorly understood.
methodsHere, we used myotubes derived from primary culture of mouse myoblasts to study the effect of citrulline on both energy metabolism and protein synthesis under different limiting conditions.
resultsWhen serum/amino acid deficiency or energy stress (mild uncoupling) were applied, citrulline stimulated muscle protein synthesis by +22% and +11%, respectively. Importantly, this increase was not associated with enhanced energy status (ATP/ADP ratio) or mitochondrial respiration. We further analysed the share of mitochondrial respiration and thus of generated ATP allocated to different metabolic pathways by using specific inhibitors. Our results indicate that addition of citrulline allocated an increased share of mitochondrially generated ATP to the protein synthesis machinery under conditions of both serum/amino acid deficiency (+28%) and energy stress (+21%). This reallocation was not because of reduced ATP supply to DNA synthesis or activities of sodium and calcium cycling ion pumps.
conclusionsUnder certain stress conditions, citrulline increases muscle protein synthesis by specifically reallocating mitochondrial fuel to the protein synthesis machinery. Because ATP/ADP ratios and thus Gibbs free energy of ATP hydrolysis remained globally constant, this reallocation may be linked to decreased activation energies of one or several ATP (and GTP)-consuming reactions involved in muscle protein synthesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.